442
Views
12
CrossRef citations to date
0
Altmetric
CLINICAL PHARMACOLOGY

Treatment of Adult Soft Tissue Sarcoma: Old Concepts, New Insights, and Potential for Drug Discovery

&
Pages 300-308 | Published online: 05 Apr 2012

REFERENCES

  • Collini P, Sorensen PH, Patel S, Blay JY, Issels RD, Maki RG, Eriksson M, del Muro XG. Sarcomas with spindle cell morphology. Semin Oncol 2009; 36(4):324–337.
  • Wagner A. Treatment of advanced soft tissue sarcoma: conventional agents and promising new drugs. J Natl Compr Canc Netw 2007; 5(4):401–410.
  • Canter RJ, Qin LX, Ferrone CR, Maki RG, Singer S, Brennan MF. Why do patients with low-grade soft tissue sarcoma die? Ann Surg Oncol 2008; 15(12):3550–3560.
  • Costa J, Wesley RA, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer 1984; 53(3):530–541.
  • Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon F, N'Guyen Bui B. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 2001; 91(10):1914–1926.
  • Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, DeLaney T, Glatstein E, Steinberg SM, Merino MJ, Rosenberg SA. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998; 16(1):197–203.
  • Davis AM, O'Sullivan B, Bell RS, Turcotte R, Catton CN, Wunder JS, Chabot P, Hammond A, Benk V, Isler M, Freeman C, Goddard K, Bezjak A, Kandel RA, Sadura A, Day A, James K, Tu D, Pater J, Zee B. Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma. J Clin Oncol 2002; 20(22):4472–4477.
  • Baldini EH, Goldberg J, Jenner C, Manola JB, Demetri GD, Fletcher CD, Singer S. Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk. J Clin Oncol 1999; 17(10):3252–3259.
  • Alektiar KM, Leung D, Zelefsky MJ, Brennan MF. Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity. J Clin Oncol 2002; 20(6):1643–1650.
  • Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 1997; 350(9092):1647–1654.
  • Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Sarcoma Meta-analysis Collaboration (SMAC). Cochrane Database Syst Rev 2000;(2):CD001419.
  • Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Cochrane Database Syst Rev 2000;(4):CD001419.
  • Pervaiz N, Colterjohn N, Farrokhyar F, Tozer R, Figueredo A, Ghert M. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer 2008; 113(3):573–581.
  • Frustaci S, Berretta M, Comandone A, Bidoli E, De Paoli A, Gherlinzoni F, De Pas T, Barbieri E, Pertici M, Apice G, Picci P. Adjuvant treatment of high-risk adult soft tissue sarcomas: a survey by the Italian Sarcoma Group. Tumori 2006; 92(2):92–97.
  • Frustaci S, De Paoli A, Bidoli E, La Mura N, Berretta M, Buonadonna A, Boz G, Gherlinzoni F. Ifosfamide in the adjuvant therapy of soft tissue sarcomas. Oncology 2003; 65 Suppl 2:80–84.
  • Mutter RW, Singer S, Zhang Z, Brennan MF, Alektiar KM. The enigma of myxofibrosarcoma of the extremity. Cancer 2011.
  • Maki RG. Gemcitabine and docetaxel in metastatic sarcoma: past, present, and future. Oncologist 2007; 12(8):999–1006.
  • Maki RG, Wathen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, Fanucchi M, Harmon DC, Schuetze SM, Reinke D, Thall PF, Benjamin RS, Baker LH, Hensley ML. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 2007; 25(19):2755–2763.
  • Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, Erba E, Grosso F, Gronchi A, Aman P, Casali P, D'Incalci M, Pilotti S, Mantovani R. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther 2009; 8(2):449–457.
  • Blay JY, von Mehren M, Samuels BL, Fanucchi MP, Ray-Coquard I, Buckley B, Gilles L, Lebedinsky C, Elsayed YA, Le Cesne A. Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma. Clin Cancer Res 2008; 14(20):6656–6662.
  • von Mehren M. Trabectedin–a targeted chemotherapy? Lancet Oncol 2007; 8(7):565–567.
  • Pires de Camargo V, van de Rijn M, Maestro R, de Alava E, Madoz-Gurpide J, Pilotti S, von Mehren M, Pedeutour F, Maki RG, Rutkowski P, Thomas DM. Other targetable sarcomas. Semin Oncol 2009; 36(4):358–371.
  • Italiano A, Cardot N, Dupre F, Monticelli I, Keslair F, Piche M, Mainguene C, Coindre JM, Pedeutour F. Gains and complex rearrangements of the 12q13–15 chromosomal region in ordinary lipomas: the “missing link” between lipomas and liposarcomas? Int J Cancer 2007; 121(2):308–315.
  • O'Cearbhaill R, Hensley ML. Optimal management of uterine leiomyosarcoma. Expert Rev Anticancer Ther 2010; 10(2):153–169.
  • Pautier P, Bui Nguyen B, Penel P, Piperno-Neumann S, Delcambre-Lair C, Bompas E, Collin F, Rey A, Jimenez M, Duffaud F. Final results of a FNCLCC French Sarcoma Group multicenter randomized phase II study of gemcitabine (G) versus gemcitabine and docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS). J Clin Oncol 2009; 25(15): abstr 10527.
  • Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer 2007; 109(9):1863–1869.
  • Cronwright G, Le Blanc K, Gotherstrom C, Darcy P, Ehnman M, Brodin B. Cancer/testis antigen expression in human mesenchymal stem cells: downregulation of SSX impairs cell migration and matrix metalloproteinase 2 expression. Cancer Res 2005; 65(6):2207–2215.
  • Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29(7):917–924.
  • Penel N, Van Glabbeke M, Marreaud S, Ouali M, Blay JY, Hohenberger P. Testing new regimens in patients with advanced soft tissue sarcoma: analysis of publications from the last 10 years. Ann Oncol 2010.
  • Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol 2008; 26(32):5269–5274.
  • Fury MG, Antonescu CR, Van Zee KJ, Brennan MF, Maki RG. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer J 2005; 11(3):241–247.
  • Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G, Kriehuber E, Diem K, Weninger W, Tschachler E, Alitalo K, Kerjaschki D. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 1999; 154(2):385–394.
  • Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010; 11(10):983–991.
  • Ryan CW, Mehren Mv, Rankin CJ, Goldblum JR, Demetri GD, Bramwell VH, Borden EC. Phase II intergroup study of sorafenib (S) in advanced soft tissue sarcomas (STS): SWOG 0505. J Clin Oncol 2008; 26(S): Abstr 10532.
  • Maki RG, D'Adamo DR, Keohan ML, Saulle M, Schuetze SM, Undevia SD, Livingston MB, Cooney MM, Hensley ML, Mita MM, Takimoto CH, Kraft AS, Elias AD, Brockstein B, Blachere NE, Edgar MA, Schwartz LH, Qin LX, Antonescu CR, Schwartz GK. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 2009; 27(19):3133–3140.
  • Agulnik M, Okuno SH, Mehren MV, Jovanovic B, Brockstein B, Benjamin RS, Evens AM. An open-label multicenter phase II study of bevacizumab for the treatment of angiosarcoma J Clin Oncol 2009; 27(15S): Abstr 10522.
  • Pastore G, Peris-Bonet R, Carli M, Martinez-Garcia C, Sanchez de Toledo J, Steliarova-Foucher E. Childhood soft tissue sarcomas incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42(13):2136–2149.
  • Pappo AS, Shapiro DN, Crist WM. Rhabdomyosarcoma. Biology and treatment. Pediatr Clin North Am 1997; 44(4):953–972.
  • Qualman SJ, Coffin CM, Newton WA, Hojo H, Triche TJ, Parham DM, Crist WM. Intergroup Rhabdomyosarcoma Study: update for pathologists. Pediatr Dev Pathol 1998; 1(6):550–561.
  • Blakely ML, Lobe TE, Anderson JR, Donaldson SS, Andrassy RJ, Parham DM, Wharam MD, Qualman SJ, Wiener ES, Grier HE, Crist WM. Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma? J Pediatr Surg 1999; 34(5):736–741; discussion 741–732.
  • Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 2010; 28(13):2151–2158.
  • Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 2002; 20(11):2672–2679.
  • Joshi D, Anderson JR, Paidas C, Breneman J, Parham DM, Crist W. Age is an independent prognostic factor in rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Pediatr Blood Cancer 2004; 42(1):64–73.
  • Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 2001; 19(12):3091–3102.
  • Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM, Heyn R, Lawrence W, Newton W, Ortega J, The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 1988; 61(2):209–220.
  • Raney RB, Maurer HM, Anderson JR, Andrassy RJ, Donaldson SS, Qualman SJ, Wharam MD, Wiener ES, Crist WM. The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS-I Through IRS-IV Studies as Background for the Current IRS-V Treatment Protocols. Sarcoma 2001; 5(1):9–15.
  • Walterhouse D, Watson A. Optimal management strategies for rhabdomyosarcoma in children. Paediatr Drugs 2007; 9(6):391–400.
  • Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1995; 13(3):610–630.
  • Arndt CA, Stoner JA, Hawkins DS, Rodeberg DA, Hayes-Jordan AA, Paidas CN, Parham DM, Teot LA, Wharam MD, Breneman JC, Donaldson SS, Anderson JR, Meyer WH. Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803. J Clin Oncol 2009; 27(31):5182–5188.
  • Weigel BJ, Breitfeld PP, Hawkins D, Crist WM, Baker KS. Role of high-dose chemotherapy with hematopoietic stem cell rescue in the treatment of metastatic or recurrent rhabdomyosarcoma. J Pediatr Hematol Oncol 2001; 23(5):272–276.
  • Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, The Intergroup Rhabdomyosarcoma Study-II. Cancer 1993; 71(5):1904–1922.
  • Shimizu A, O'Brien KP, Sjoblom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 1999; 59(15):3719–3723.
  • Sjoblom T, Shimizu A, O'Brien KP, Pietras K,Dal Cin P, Buchdunger E, Dumanski JP, Ostman A, Heldin CH. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 2001; 61(15):5778–5783.
  • McArthur G. Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol 2007; 14(10):2876–2886.
  • Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 2010; 28(10):1772–1779.
  • West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D, van de Rijn M. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A 2006; 103(3):690–695.
  • Blay JY, El Sayadi H, Thiesse P, Garret J, Ray-Coquard I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol 2008; 19(4):821–822.
  • Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, Kwiatkowski DJ, Maki RG. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010; 28(5):835–840.
  • Alman BA, Li C, Pajerski ME, Diaz-Cano S, Wolfe HJ. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol 1997; 151(2):329–334.
  • Davies DR, Armstrong JG, Thakker N, Horner K, Guy SP, Clancy T, Sloan P, Blair V, Dodd C, Warnes TW, Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. Am J Hum Genet 1995; 57(5):1151–1158.
  • Couture J, Mitri A, Lagace R, Smits R, Berk T, Bouchard HL, Fodde R, Alman B, Bapat B. A germline mutation at the extreme 3’ end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor. Clin Genet 2000; 57(3):205–212.
  • Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E, Warneke CL, Lopez-Terrada D, Pollock RE, Lev D. Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 2008; 173(5):1518–1527.
  • Hansmann A, Adolph C, Vogel T, Unger A, Moeslein G. High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer 2004; 100(3):612–620.
  • Azzarelli A, Gronchi A, Bertulli R, Tesoro JD, Baratti D, Pennacchioli E, Dileo P, Rasponi A, Ferrari A, Pilotti S, Casali PG. Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis. Cancer 2001; 92(5):1259–1264.
  • Chao AS, Lai CH, Hsueh S, Chen CS, Yang YC, Soong YK. Successful treatment of recurrent pelvic desmoid tumour with tamoxifen: case report. Hum Reprod 2000; 15(2):311–313.
  • Benson JR, Mokbel K, Baum M. Management of desmoid tumours including a case report of toremifene. Ann Oncol 1994; 5(2):173–177.
  • Leithner A, Schnack B, Katterschafka T, Wiltschke C, Amann G, Windhager R, Kotz R, Zielinski CC. Treatment of extra-abdominal desmoid tumors with interferon-alpha with or without tretinoin. J Surg Oncol 2000; 73(1):21–25.
  • Gounder M, Lefkowitz RA, Keohan ML, D'Adamo DR, Hameed M, Antonescu CR, Singer S, Stout K, Ahn L, Maki RG. Activity of sorafenib against desmoid tumor/deep fibromatoses. Clin Cancer Res 2011.
  • Patel SR, Evans HL, Benjamin RS. Combination chemotherapy in adult desmoid tumors. Cancer 1993; 72(11):3244–3247.
  • de Camargo VP, Keohan ML, D'Adamo DR, Antonescu CR, Brennan MF, Singer S, Ahn LS, Maki RG. Clinical outcomes of systemic therapy for patients with deep fibromatosis (desmoid tumor). Cancer 2010; 116(9):2258–2265.
  • Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347(7):472–480.
  • Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, Corless CL, Debiec-Rychter M, DeMatteo RP, Ettinger DS, Fisher GA, Fletcher CD, Gronchi A, Hohenberger P, Hughes M, Joensuu H, Judson I, Le Cesne A, Maki RG, Morse M, Pappo AS, Pisters PW, Raut CP, Reichardt P, Tyler DS, Van den Abbeele AD, von Mehren M, Wayne JD, Zalcberg J. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)–update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 2007; 5 Suppl 2:S1–29; quiz S30.
  • Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373(9669):1097–1104.
  • Joensuu H, Eriksson M, Hatrmann J, Sundby Hall K, Schutte J, Reichardt A, Schlemmer M, Wardelmann E, Ramadori G, Al-Batran S, Nilsson BE, Monge O, Kallio R, Sarlomo-Rikala M, Bono P, Leinonen M, Hohenberger P, Alvegard T, Reichardt P. Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO). J Clin Oncol 2011; 29: Abstr LBA1.
  • Gounder MM, Maki RG. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chemother Pharmacol 2010; 67 Suppl 1:S25–43.
  • Maki RG. Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J Clin Oncol 2010; 28(33):4985–4995.
  • Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998; 351(9113):1393–1396.
  • Chan JM, Stampfer MJ, Ma J, Gann P, Gaziano JM, Pollak M, Giovannucci E. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst 2002; 94(14):1099–1106.
  • Ayalon D, Glaser T, Werner H. Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein. Growth Horm IGF Res 2001; 11(5):289–297.
  • Wan X, Helman LJ. The biology behind mTOR inhibition in sarcoma. Oncologist 2007; 12(8):1007–1018.
  • Wan X, Shen N, Mendoza A, Khanna C, Helman LJ. CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling. Neoplasia 2006; 8(5):394–401.
  • Wan X, Mendoza A, Khanna C, Helman LJ. Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res 2005; 65(6):2406–2411.
  • Chawla SP, Tolcher AW, Staddon AP, Schuetze S, D'Amato GZ, Blay JY, Loewy J, Kan R, Demetri GD. Survival results with AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas: Update of phase II trial. J Clin Oncol 2007; 25(18S): Abstr 10076.
  • Chawla SP, Blay J, Ray-Coquard IL, Le Cesne A, Staddon AP, Milhem MM, Penel N, Riedel RF, Bui Nguyen B, Cranmer LD, Reichardt P, Bompas E, Song Y, Lee R, Eid JE, Loewy J, Haluska FG, Dodion PF, Demetri GD. Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT). J Clin Oncol 2011; 29: abstr 10005.
  • Stacchiotti S, Negri T, Zaffaroni N, Palassini E, Morosi C, Brich S, Conca E, Bozzi F, Cassinelli G, Gronchi A, Casali PG, Pilotti S. Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect. Ann Oncol 2011; 22(7):1682–1690.
  • Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303(5659):844–848.
  • Ray-Coquard IL, Blay J, Italiano A, Cesne AL, Penel N, Zhi J, Beryozkina A, Heil F, Rueger R, Nichols GL, Nguyen BB. Neoadjuvant MDM2 antagonist RG7112 for well-differentiated and dedifferentiated liposarcomas (WD/DD LPS): A pharmacodynamic (PD) biomarker study. J Clin Oncol 2011; 29(S): Abstr 10007b.
  • Butrynski JE, D'Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Janne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 2010; 363(18):1727–1733.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.